Variant 8-72023917-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000262209.5(TRPA1):c.3052-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,551,724 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 5 hom. )

Consequence

TRPA1
ENST00000262209.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.000009181

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.814

Variant links:

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

TRPA1 links:

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

MSC-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-72023917-G-A is Benign according to our data. Variant chr8-72023917-G-A is described in ClinVar as [Benign]. Clinvar id is 3025034.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 539 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPA1	NM_007332.3 linkuse as main transcript	c.3052-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262209.5	NP_015628.2
MSC-AS1	NR_033652.1 linkuse as main transcript	n.1029-28622G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPA1	ENST00000262209.5 linkuse as main transcript	c.3052-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007332.3	ENSP00000262209	P1
MSC-AS1	ENST00000518916.5 linkuse as main transcript	n.392-28622G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00127

AC:

315

AN:

248706

Hom.:

AF XY:

0.00104

AC XY:

140

AN XY:

134450

show subpopulations

Gnomad AFR exome

AF:

0.0139

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000356

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000719

AC:

1006

AN:

1399544

Hom.:

Cov.:

AF XY:

0.000619

AC XY:

433

AN XY:

699602

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.00146

Gnomad4 ASJ exome

AF:

0.0000391

Gnomad4 EAS exome

AF:

0.000640

Gnomad4 SAS exome

AF:

0.000201

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000428

Gnomad4 OTH exome

AF:

0.000982

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152180

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

261

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0120

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00239

Hom.:

Bravo

AF:

0.00418

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

TRPA1: BS1 -

TRPA1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000092

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: -44

DS_AL_spliceai

0.24

Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over